Background: Warfarin has been the cornerstone of therapy for patients with stage 4 and 5 chronic kidney disease (CKD) requiring anticoagulation. These patients were omitted from landmark clinical trials involving apixaban. Apixaban’s safety profile is still largely unclear in this population. Objectives: To compare major bleeding, secondary bleeding outcomes, stroke, and thromboembolism in veterans with CKD stage 4, with CKD stage 5, and on dialysis on apixaban or warfarin. Methods: A retrospective chart review identified veterans with CKD stage 4 and stage 5, and on dialysis who received either apixaban or warfarin from 2013 to 2019 at the Memphis Veterans Affairs Medical Center. The primary outcome was incidence of major bleeding. Secondary outcomes were clinically relevant nonmajor and minor bleeding, composite bleeding, venous thromboembolism (VTE), and stroke. Results: A total of 111 patients were included in this study (warfarin group, n = 57; apixaban group, n = 54). Primary and secondary outcomes were analyzed using the χ2 or Fisher exact tests as appropriate. There was no difference in major bleeding between groups (14% vs 7%, P = 0.362). There were increased rates of minor bleeding (26% vs 6%, P = 0.004) and composite bleeding (46% vs 20%, P = 0.004) in patients receiving warfarin. There were no differences in rates of stroke or VTE between the 2 groups. Conclusion and Relevance: There was no difference in major bleeding in patients who received apixaban compared with warfarin. Apixaban may be a reasonable alternative to warfarin in veterans with CKD stage 4 and 5, including those on dialysis.
The endocrine pancreas of larval lampreys appears as islets of cells isolated in the submucosa and those both continuous with, and within, the gut epithelium at the intestinal-oesophageal-bile duct junction. The islets, and occasionally follicles, are composed of only insulin-secreting (B) cells. During metamorphosis, the bile duct either completely degenerates or its epithelium transforms into a caudal endocrine pancreas while a cranial pancreas appears as a specialization and expansion of the larval pancreas. Immunocytochemistry and histochemistry demonstrates that there is a wide variation in the distribution of the pancreatic tissue in adults of lamprey species, and this variation may result from interspecific differences in morphogenetic events at metamorphosis. Despite species variability in its distribution, the endocrine pancreatic tissue in all adult lampreys is composed of equal numbers of B cells and somatostatin-secreting (D) cells, but there are no glucagon-secreting (A) cells. Immunocytochemistry reveals that B and D cells of the caudal pancreas differentiate from cells of the larval bile duct during metamorphosis of the sea lamprey,Petromyzon marinus.
Immunocytochemistry with protein A-gold and routine electron microscopy were used to identify cell types within the endocrine pancreas of larvae, juvenile adults, and upstream-migrant adults of the sea lamprey, Petromyzon marinus. The larval pancreatic islets are composed only of insulin-immunoreactive B-cells, which are uniform in their fine structure. The cranial and caudal pancreatic tissue in both adult periods contains three cell types: B-cells, somatostatin-immunoreactive D-cells, and a third cell type of unknown content. No glucagon-immunoreactive cells are present in lampreys, but B- and D-cells exist in equal numbers in the pancreatic tissue of adults. The B-cells of adults have a fine structure similar to those in larvae. D-cells have secretory granules that are distinctly different from those both in B-cells and in the third cell type. Although B- and D-cells in lamprey pancreatic tissues have a basic morphological similarity to these cells in other vertebrates, their granules are generally of smaller dimensions. The inclusion of granules within large pleomorphic bodies in many D-cells indicates that granule turnover is common. Immunocytochemistry will be a useful tool for showing the relationship between the cells in the degenerating bile ducts and those of the developing adult pancreas.
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